The high-throughput screening of vast numbers of compounds is pivotal to the drug discovery process. It is often an expensive, timely, process which can return false positive results. What sets us apart is our specific high-throughput screening knowledge and experience across multiple ion channel targets.

By working with our ion channel high-throughput screening specialists, you will have access to a dedicated and highly experienced team to support hit finding campaigns, hit-to-lead activities, lead optimisation with follow-up selectivity profiling. Custom cell line generation, assay development and optimisation is also provided in-house.

Once we have run your project, we will interpret the data, communicate the results and support your decision making to best inform your screening strategy.

Our complementary phenotypic and translational assays enable further detailed characterisation of your lead compounds.

Figure 1. Screening against V434L KCNC1 using thallium flux assay. Read the drug repurposing high-throughput screeningcase study about a recent project researching a rare de novo variant in the KCNC1 gene.

To support your medicinal chemistry programmes and structure-activity relationship (SAR) studies, we offer access to commercially available compound libraries from Enamine and Assay.Works.

Our approach enabled a long-term Kv1.3 screening project to expand medicinal chemistry SAR and successfully identify selective small molecule modulators by accessing high quality APC and ion channel expertise. Through this long-term collaboration with a pharmaceutical company, Metrion delivered: exceptional long-term reliability of the optimised primary target screen and counter-screen assays over the course of two years, bespoke development of cell lines, including support of complete gene family selectivity and species selectivity studies, wider selectivity studies including extended cardiac (CiPA) panel screening, and exploration of mechanism of action (e.g. closed, open or inactivated state block).

Figure 2: Physico-chemical property profile of Assay.Works library according to Lipinski’s Rule of 5 (left); Prediction of compound properties and drug-like features: Colloidal Aggregation, Permeability, Bioavailability, Solubility, PAINS.

Figure 3: Assay.Works compound sets and diversity metrics based on Bemis-Murcko clusters.

By screening across multiple platforms, including fluorescence (FLIPR) and automated electrophysiology (Qube) instruments synergistically, we offer flexibility to progress your project as efficiently and cost-effectively as possible.